Synovial tissue in Lyme arthritis can histologically resemble rheumatoid synovitis, particularly the prominent infiltration of T lymphocytes. This has raised speculation whether Lyme synovitis represents an on- going response to the causative spirochete, Borrelia burgdorferi, or rather a self-perpetuating autoimmune reaction. The current study examined the repertoire of infiltrating T cells in Lyme arthritis synovial fluid to determine the degree of bias of the T cell antigen receptor (TCR) beta-chain Variable (VB) region, and whether this was provoked by B. burgdorferi. Using a highly sensitive and consistent quantitative PCR technique, a comparison of the TCR-VB repertoire between peripheral blood and synovial fluid showed an increased expression of VB2 and VB6. This is remarkably similar to our previous findings in rheumatiod arthritis. However, activation of synovial fluid T-cells with B. burgdorferi caused a profound proliferation and shifted the TCR repetoire toward expression of VB13.1. Collectively, the findings suggest that B. burgdorferi-induced proliferation of Lyme arthritis synovial T cells results in TCR-VB bias, although the skewing observed in fresh synovial fluid may reflect more a synovial-trophic or inflammatory response, rather than a specific Borrelia reaction. Data have been analyzed using the CDMAS resource.